This invention relates to an improved process for purifying a natural product using a two-phase, multi-solvent system followed by back extraction and precipitation. The method allows for the removal of impurities by controlling the polarity balance of a two-phase system by manipulating the proportions of the solvents. The choice of the solvent composition allows for the product to enter and exit the process in the same solvent from which it can be isolated in a solid form. Prior processes in the isolation and purification of similar natural products required chromatography steps. This process allows for recovery of the product in the same solvent used for the extraction steps. Additionally, this method reduces the overall solvent consumption making the process economically viable for commercial use.
This invention is directed to a process for purifying a natural product after initial isolation by whole broth extraction using a two-phase, multi-solvent system after initial isolation by whole broth extraction. Recovery of the product from the back extraction step involves additional vacuum concentration and a two-stage precipitation step. Typically three or more solvents are employed since the multi-solvent system can impact the relative polarity balance of the solution in which the compound is being purified. The process of the invention can be used to purify lipophilic natural products such as echinocandin-type cyclic peptides. In particular, there is disclosed a process for purifying pneumocandin Compound I of the formula 
which is the starting material for the antifungal compound of the formula 
This compound has been found useful in treating fungal infections and for the treatment and prevention of infections caused by Pneumocystis carinii, which are often found in immunocompromised patients such as those suffering with AIDS. Compound I is disclosed and claimed in U.S. Pat. No. 5,194,377, which issued Mar. 16, 1993. Compound II is disclosed and claimed in U.S. Pat. No. 5,378,804, which issued Jan. 3, 1995.